title: Comparison of epigenetic profiles of human oral epithelial cells from HIV-positive (on HAART) and HIV-negative subjects.
abstract: HIV-infected subjects on highly active antiretroviral therapy (HAART) are susceptible to comorbid microbial infections in the oral cavity. We observed that primary oral epithelial cells (POECs) isolated from HIV+ subjects on HAART grow more slowly and are less innate immune responsive to microbial challenge when compared with POECs from normal subjects. These aberrant cells also demonstrate epigenetic differences that include reduction in histone deacetylase 1 (HDAC-1) levels and reduced total DNA methyltransferase (DNMT) activity specific to enzymes DNMT1 and DNMT3A. The DNMT activity correlates well with global DNA methylation, indicating that aberrant DNMT activity in HIV+ (on HAART) POECs leads to an aberrantly methylated epithelial cell phenotype. Overall, our results lead us to hypothesize that, in patients with chronic HIV infection on HAART, epigenetic changes in key genes result in increased vulnerability to microbial infection in the oral cavity.
authors.affiliation: Department of Biological Sciences, Case Western Reserve University, Cleveland, OH, USA. skg12@case.edu
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Thomas S
authors.initials: TS
authors.lastname: McCormick
authors.forename: Betty L
authors.initials: BL
authors.lastname: Eapen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yohannes
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
authors.forename: Aaron
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D049109:Cell Proliferation; D002469:Cell Separation; D002473:Cell Wall / Q000737:chemistry; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016967:Fusobacterium nucleatum / Q000378:metabolism; D006679:HIV Seropositivity / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D006801:Humans; D009055:Mouth / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human
keywords: DNMTs; HAART; HDAC-1; HIV; hBD-2; oral epithelium